Gender specific effects on the actin-remodelling protein Flightless I and TGF-beta 1 contribute to impaired wound healing in aged skin

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dc.contributor.authorAdams, D.
dc.contributor.authorStudwick, X.
dc.contributor.authorKopeki, Z.
dc.contributor.authorHooper-Jones, J.
dc.contributor.authorMatthaei, K.
dc.contributor.authorCampbell, H.
dc.contributor.authorPowell, B.
dc.contributor.authorCowin, A.
dc.date.issued2008
dc.description.abstractImpaired wound healing in the elderly presents a major clinical challenge. Understanding the cellular mechanisms behind age-related impaired healing is vital for developing new wound therapies. Here we show that the actin-remodelling protein, Flightless I (FliI) is a contributing factor to the poor healing observed in elderly skin and that gender plays a major role in this process. Using young and aged, wild-type and FliI overexpressing mice we found that aging significantly elevated FliI expression in the epidermis and wound matrix. Aging exacerbated the negative effect of FliI on wound repair and wounds in aged FliI transgenic mice were larger with delayed reepithelialisation. When the effect of gender was further analysed, despite increased FliI expression in young and aged male and female mice, female FliI transgenic mice had the most severe wound healing phenotype suggesting that male mice were refractory to FliI gene expression. Of potential importance, males, but not females, up-regulated transforming growth factor-beta1 and this was most pronounced in aged male FliI overexpressing wounds. As FliI also functions as a co-activator of the estrogen nuclear receptor, increasing concentrations of beta-estradiol were added to skin fibroblasts and keratinocytes and significantly enhanced FliI expression and translocation of FliI from the cytoplasm to the nucleus was observed. FliI further inhibited estrogen-mediated collagen I secretion suggesting a mechanism via which FliI may directly affect provisional matrix synthesis. In summary, FliI is a contributing factor to impaired healing and strategies aimed at decreasing FliI levels in elderly skin may improve wound repair.
dc.description.statementofresponsibilityDamian H. Adams, Xanthe L. Strudwick, Zlatko Kopecki, Jane A. Hooper-Jones, Klaus I. Matthaei, Hugh D. Campbell, Barry C. Powella and Allison J. Cowin
dc.description.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/395/description#description
dc.identifier.citationThe International Journal of Biochemistry and Cell Biology, 2008; 40(8):1555-1569
dc.identifier.doi10.1016/j.biocel.2007.11.024
dc.identifier.issn1357-2725
dc.identifier.issn1878-5875
dc.identifier.orcidCowin, A. [0000-0003-2885-2080]
dc.identifier.urihttp://hdl.handle.net/2440/51914
dc.language.isoen
dc.publisherPergamon-Elsevier Science Ltd
dc.source.urihttps://doi.org/10.1016/j.biocel.2007.11.024
dc.subjectCell Nucleus
dc.subjectCytoplasm
dc.subjectFibroblasts
dc.subjectAnimals
dc.subjectMice, Transgenic
dc.subjectHumans
dc.subjectMice
dc.subjectEstradiol
dc.subjectMicrofilament Proteins
dc.subjectCarrier Proteins
dc.subjectCytoskeletal Proteins
dc.subjectTrans-Activators
dc.subjectSex Factors
dc.subjectWound Healing
dc.subjectUp-Regulation
dc.subjectProtein Transport
dc.subjectAging
dc.subjectFemale
dc.subjectMale
dc.subjectTransforming Growth Factor beta1
dc.titleGender specific effects on the actin-remodelling protein Flightless I and TGF-beta 1 contribute to impaired wound healing in aged skin
dc.typeJournal article
pubs.publication-statusPublished

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